The complement (C) system is assumed to often play a pathologic role in the inflammatory and immunologically-mediated damage seen in renal disease. Previous work from this laboratory demonstrates that damaged (but not normal) kidney cells can cause cell dependent, non-immunologic activation of C indicating that 'altered' kidney cells may become alternative C pathway activators. Their contribution to the initiation or enhancement of C activity may be a previously unrecognized factor in disease production. We will investigate the interactions of the C proteins with normal and altered, damaged, or killed kidney cells. Primary tissue cell cultures of human and rat renal cortical tissue will be used to establish and characterize an in vitro model. This system will be used to determine the interactions of normal kidney cells with C and to determine the effects these interactions have on various leukocyte populations. These results will be compared to those obtained when kidney cells have been killed, or pretreated with surface modifying enzymes, or metabolic inhibitors. The role of antibody in 'non-immunologically'-induced C activation by the altered kidney cells will be assessed. Sensitive, quantitative hemolytic assays, immunofluorescent binding studies, and immunochemical measurements will be made to evaluate C activity. Established cell culture techniques and standard methods for isolating and evaluating the function and activation of leukocyte populations will be employed. Normal kidney cells are used in these studies because of our primary interest in the role of the C system in inflammatory renal disease. However, the insights gained may further understanding of how other types of nucleated cells (normal or 'altered') interact with the C system, what conditions result in loss of normal interactions, and what events lead to reestablishment of homeostasis or to an escalated inflammatory response. The results of these investigations should be of importance to the basic scientist dissecting the factors contributing to inflammation and to the clinician trying to establish protocols for prevention and abatement of ongoing renal disease.